biomed week 8 Flashcards
1
Q
light microscopy can visualize structures as small as
A
0.2 microns
2
Q
what are the two different types of microscopes
A
fluorescence and confocal
3
Q
confocal microscopy can view
A
cell or tissue in a particular plane
4
Q
electron microscopy can visualize structures as small as ….. the tissue are often ….. in …….. …….
A
3nm
frozen, liquid nitrogen
5
Q
tissues and cells viewed in microscopes are always
A
dead
6
Q
what is fixation?
A
chemicals cross-link proteins and inactivate
enzymes that degrade cells/cellular components
However, chemical characteristics of molecules are
mostly retained so that staining the tissue still occurs
7
Q
what is Dehydration & clearing
A
tissues are passed through alcohol
solutions (replaces the water) and then the alcohol is
removed
8
Q
what is Infiltration and embedding
A
the tissue is infiltrated with a
substance (i.e. paraffin wax) and then allowed to harden
9
Q
what is Trimming in histology
A
tissue is sliced into thin, almost transparent
slices using a microtome
10
Q
what is Hematoxylin and eosin
A
usually both done together in a
tissue preparation
Hematoxylin is a dark blue basic dye, and will bind to negatively-charged molecules
- Molecules that bind to basic dyes are known as
basophilic molecules
Eosin is a pink acidic dye – it binds to positively-charged molecules (i.e. cytosolic proteins)
- Eosin is acidophilic
11
Q
Periodic acid-Schiff stain is great at showing what?
A
glycogen and many glycoproteins
12
Q
what cell/ organelle is hematoxylin highlighted in
A
nucleus
13
Q
what cell/organelle is eosin highlighted in
A
nucleus
14
Q
what organelle/ cell is PAS highlighted in
A
cytosol, mucous some ECM
15
Q
what is the trichrome stain? what organelle cell is highlighted?
A
Keratin, collagen, DNA, cytoplasmic proteins
Muscle fibres, nuclei, collagen –complicated stain
16
Q
why is histology useful?
A
At the junction of anatomy and physiology
Much of the function of a cell or tissue can be deduced by its microscopic structure
17
Q
where are simple squamous cells found
A
air sacs of lungs, lining of the heart, blood vessels and lymphatic vessles,
allows materials to pass through with diffusion (exchange epithelium
18
Q
simple cubodial epithilium cells are found where
A
in ducts and secretory portions of small glands in the kidney tubules
function: secretes and absorbs, transport epitilium
19
Q
simple columbar epithelium where is it found?
A
microvilli in the GI tract
secretes mucous and enzymes
- increases surface area and absorption
20
Q
pesudostratified columnar epithelium function and location
A
cilliated tissue that lines the brochii, trachea and much of the upper respiratory tract
secretes mucous
21
Q
stratified squamous epithelium function and location
A
lines the esophagus, vagina and mouth
skin
protects against abrasion
22
Q
transitional epithelium function and location
A
lines the bladder, urethra, urinary tract
allows them to expand and stretch
- chemical protection from urine
23
Q
what is paracellular movement
A
between epithelial cells, movement across junctions
24
Q
what is transcellular movement
A
through epithelial cells, movement across apical and basolateral cell membranes
25
flat cell is called
squamous
26
a square cell is called
cuboidal
27
a tall cell is called
columbar
28
only one layer of cells is called
simple
29
what are multiple layered cells called
stratified
30
Stratified epithelia (i.e. skin) is named based on the shape of the
cell farthest from the base
31
even though there are cuboidal cells at the base of the epidermis, the cells at the “top” are flattened therefore it is called ....
stratified squamous epithelium
32
If there are cilia…
then it’s a ciliated epithelium
33
Actin filaments are for
shape and motility of
the cell
34
Intermediate filaments do what for the cell
structural
“strength” to the cell
* Desmin, keratin
35
Microtubules determine ....
polarity, cell division, movement of cilia (if
present)
36
what are tight junctions
Located at the apical aspect
of almost all epithelial cells
37
where are tight junctions found
Found in the gut, brain,
skin, respiratory tract
§ Closest to the lumen of
all the junctions
38
what are the key functions of tight junctions
Barrier that prevents movement of undesirable
substances to the tissues below
Regulates the movement of a variety of molecules
between cells, through the barrier
Helps establish polarity – TJs seem to help direct membrane proteins to the apical vs. basolateral sides
39
what are the key proteins in tight junctions
Claudins – trans-membrane proteins that can act as channels
- for small molecules (paracellular)
- Some are permeable (Claudin2), some are relatively
impermeable (Claudin-1)
Occludin – trans-membrane protein, function not clear
Junctional adhesion molecules (JAM)
- Trans-membrane protein that may
mediate permeability to larger molecules
ZO-proteins
- Important in tight junction formation,
interact with the cytoskeleton
40
what is the structure of tight junctions
- Claudins and JAMs are transmembrane proteins
- extend into the extracellular space
and bind to claudins and JAMs on the
neighbouring cells
- ZO proteins bind to the intracellular face
of claudins and JAMs, linking them to
the actin cytoskeleton underneath
- Cell membrane proteins, even lipids
seem unable to cross the “belt” of the
TJs
- Keeps basolateral and apical cell
membrane components separated
41
where are adherens junctions typically found
Found immediately below tight junctions
42
what is the function of adheres junctions
- Strengthens and
stabilizes tight junctions
- Participates in cell-cell
signaling that regulates
cell division and
proliferation
43
what are the key proteins in adheres junctions
Cadherin – transmembrane protein that
interacts with other cadherins on the
neighbouring cell (similar to claudins)
Catenins – linker molecules that connect the
intracellular face of claudins to the actin
cytoskeleton
- Beta catenin can also act as a signal
- When cadherins connect across cells,
beta-catenin remains associated with
cadherins
- When they don’t connect, beta-catenin
can dissociate and signal cell division
44
how might adherens junctions (beta catenin) regulate wound healing?
send signals that we need more catherin to be made to bridge gap between epithelial cells
when there is an injury, the cll might die off, the connection will be lost, if lost beta catenin will signal that we need more proteins and cell division
45
epithelial cells have blood vessels
false, they are avascular
46
adherns junctions and tight junctions circle ......
the entire apical aspect of a colunar of cuboidal cells
47
desmosomes only attach to ....
certain spots on the epithelial cell membrane
48
what are the key similarities of desmosomes versus adheres junctions
- Strong adhesion between cells
- Desmosomes use cadherin-like
molecules
- Both have intracellular
“plaques” that interact with
proteins that can act as
“signalers” and “linkers” (i.e.
beta-catenin)
49
what are the key differences between desmosomes and adheres junctions
- Desmosomes connect to
intracellular intermediate
filaments (i.e. keratin)
- Desmosomes provide more
structural stability to the cell
50
what are significant differences between desmosomes and hemidesmosomes
- Transmembrane “linking” protein is an integrin, not a claudin-like molecule
- Integrin binds to a component of the basement membrane known as laminin
-Does not bind to a molecule on an adjacent cell
- Hemidesmosomes do not seem to have important intracellular signaling functions
- Hemidesmosomes do link to intracellular intermediate filaments
51
what is the function of hemidesmosomes
adhesion of the epithelial cell to the basement membrane
52
barrier that restricts movement of substances apical to basal
tight junctions
53
Transport of substances from the apical side to the basal side of the epithelium is what type of junction?
tight junctions, claudins
54
strength of the epithelial lining
adherens , desmosomes
55
Determination of polarity (apical vs. basal) across the
epithelial cell
tight junction
56
Signaling and regulation of the activity of the epithelial cell
adheres, gap junctions
57
Anchoring the epithelial cell to the underlying connective tissue
hemidesmosomes
58
cillia have a ........ structure of microtubules , with a central doublet
9+2
- Bound to a basal body-like structure
at the apex of the membrane – also
composed of microtubules
(axoneme)
59
Almost all cells – including epithelial cells - have one primary cilia These are non-motile cilia that have a
ring of 9
microtubular structures, but no central doublet
Very long – range from 1 – 10 microns (much longer
than microvilli)
60
The primary cilia have a range of receptors and intracellular signaling mechanisms that communicate information from the external environment to the cell
why is this important?
Extremely important in development of the embryo,
sensing fluid movements, and sensing the presence of
growth factors
61
loose connective tissue is usually found
often found beneath the epithelial lining of many tissues
- Lamina propria of the intestine,
respiratory tract
- Can also be found as “packing” between
muscle fibres, within nerves, etc.
Lots of ground substance, many cells, relatively little
collagen
62
Dense irregular connective tissue has .............
Fewer cells, less ground substance than loose connective tissue
Much more collagen
- Collagen is arrayed in bundles
that are not parallel, but
arranged in many different
directions
- Resists stresses from multiple
different directions
Found in capsules that surround organs and in the dermis
63
Dense regular connective tissue consists of
- Lots of collagen (type I) with less ground
substance and cells than loose connective
tissue
- Collagen is oriented in one particular
direction
- Resists stresses along one line or plane
* Typical examples – tendons, ligaments,
aponeuroses
64
Collagen consisits of
fibroblasts
* Different types of collagen have
different functions
Type 1 – resists tension, multiple
triple helices bound together to
form fibrils, and fibrils are
organized to form fibres
-Major collagen type in dense CT
and bone
65
Type II collagen is
smaller fibrils with less organized orientation
than dense regular tissue
66
type 3 collagen is
reticular fibres
§ Major component of loose connective tissue
67
Type I, II, and III collagens are known as
fibrillar collagens
68
Type IV collagen – forms the basement membrane that connects
epithelial and connective tissue layers
- Forms a sort of cross-linked “net” with laminin
(glycoprotein) and proteoglycans interspersed within it
69
Type IV Collagen in the Basement Membrane
The basement membrane is formed from an organized meshwork of type IV collagen, proteoglycans, and laminin
Note that integrins (hemidesmosomes) bind to the
laminin in the basement membrane
70
Connective Tissue Proper – Ground
Substance
Two major components:
Multi-adhesive glycoproteins
Proteoglycans
71
Multi-adhesive glycoproteins bind to
a wide variety of components of the extracellular matrix
ex
- laminin binds to type IV collagen and the integrins of hemidesmosomes
- Fibronectin binds to collagen, glycosaminoglycans (GAGs) on proteoglycans, and some integrins
72
describe the Proteoglycans – 3-part structure:
- A very long, linear polymer of hyaluronic acid (a GAG)
- Linking proteins attached to the hyaluronic acid polymer
- Shorter GAG chains attached to the linking proteins
73
Proteoglycans are highly ..............
An ECM rich in proteoglycans is
difficult for .........
proteoglycans store ........
hydrated “collect” water in
the ECM due to the OH-groups on
the carbohydrate GAGs
most bacteria to penetrate
“Store” of growth factors
- Messengers can be “stored”
within the ECM – associated
with proteoglycans
-- When the ECM is broken
down, these factors are
liberated à replacement of
the ECM
74
what are some common pathology sources of the epithelium
-Disrupted barrier or protective function of the epithelial lining
- Disrupted transport across the epithelial lining
-Inflammation in the connective tissue below the epithelium
* Due to autoimmune or allergic conditions
* Due to infection
- Malignant transformation of epithelial cells
75
what epithelial tissue is the skin made up of
Stratified squamous epithelium
76
what are the typical functions of stratified squamous epithelium
protection against abrasion, they are dead in the coreum
77
Apical layers – cells that accumulate
keratin, “compact” it, and eventually
die
78
Keratin = main intermediate filament in
keratinocytes
79
Keratin is strong and forms bundles –
a barrier that prevents water loss from
deeper layers and microbe invasion
80
keratin complexes with another protein called
filaggrin
– that helps compact keratin
and attracts water, aiding in skin
moisturization
81
as skin matures from deeper layers ...... which causes ......... what is the net result?
junctions are modified
- Loss of hemidesmosomes (no contact with the basement membrane)
- Modification of desmosomes
- Tight junctions remain
Net result – the “outside” surface
of the skin is flattened layers of
dead “bags” of keratin and
filaggrin linked by tight junctions
82
what is the dermal layer
- Dense irregular connective tissue
-Capillary loops extend from the papillary dermis, bringing nutrients and exchanging gases and wastes
- Dermal vasculature allows immune cells to enter the
epidermis
- Fight infection
- Heal wounds
83
what is Atopic dermatitis
One of the most common skin conditions
Typical symptoms & signs:
§ Itchy papules and plaques that can
become excoriated with scratching
§ Distributed over the extensor
surfaces, face, and scalp
§ Worsen in response to allergen
exposure
Highly heritable – children of parents with atopic dermatitis have
§ Subtle abnormalities in filaggrin impair the ability of the more
apical strata to retain the moisture of the skin
§ Tight junction changes to more permeable types decrease the
barrier function of the skin
84
Postulated sequence of events of atopic dermatitis
Impaired skin barrier -> repeated introduction of antigens to immune cells that reside in the epidermis and the dermis ->
recruitment of other, particular immune cells into the dermis and epidermis from the blood stream -> a specific type of inflammation (type 2) that causes excessive histamine release into the skin -> chronic swelling and itch with further antigen
exposure
85
The Intestinal Mucosa –
General Structure
Simple columnar epithelium – prominent apical microvilli
- Specialized for absorption of
nutrients and water
Interspersed with cells that have
glandular functions
- Many of these secrete mucous
(known as goblet cells)
- Mucous has a protective and a
digestive role
86
the intestinal mucosa epithelial layer sits on a bed of
highly vascularized loose connective tissue known as the
lamina propria
87
Blood and lymphatic capillaries causes
absorption of nutrients and water
from across the epithelial cell into
blood
88
Immune cells are present in the inestinal mucosa
layer which functions as
protection from hostile microbes and tolerance to healthy microbes
89
in the intestinal mucosa the Layer of smooth muscle – the muscularis mucosa is important for
maintain the shape of the structure
90
Finger-like projection of epithelium
and lamina propria of the intestinal mucosa are called
the villus
91
Paracellular route
between adjacent
enterocytes - mostly regulated by tight
junctions
92
Transcellular route
through enterocytes,
across cell membranes – regulated by
membrane proteins
93
paracellular route of celiac disease
Gliadin binds to a protein (FYI – chemokine
receptor CXCR3)
signaling cascade that causes release of a
signalling protein called zonulin
Zonulin release leads to phosphorylation of
ZO proteins
disassembly of claudin and occludin proteins
at the tight junction
leakage of gliadin into the immune cell- containing lamina propria
94
what are the main functions of the skin
- Protective barrier
Mechanical, chemical or
thermal injuries
- Important barrier to
infection
- Reduces heat, fluid,
electrolyte loss
- Key for regulating body
temperature
- Provides sensory
information
- Limited importance in waste removal and vitamin synthesis (vitamin D)
95
what are the three layers of the skin
- epidermis
- dermis
- subcutaneous
96
what are the varies of thickness of the skin
Thick – palms and soles
Epidermis is 0.4 – 1.4
mm thick
Thin – everywhere else
Epidermis is 0.075 – 0.15
mm
97
what are the epidermal layers from outermost to innermost
- Stratum corneum
* Stratum lucidum
only in thick skin
* Stratum granulosum
* Stratum spinosum
* Stratum basale
98
what are some characteristics of the stratum coreum
most superficial
layer size - 15-30 cell layers
most important component of the barrier
- prevents penetration of microbes
- prevents dehydration
- mechanical protection
skin cells in this layer are dead and full of keratin and filaggrin
- held together by tight juinctions, desmosomes
- filaggrin helps keratin aggregate into large macrofibrils
99
what are some characteristics of stratum lucidum
immediately below s corneum
- only found in thick skin of the palms, soles and digits
3-5 cell layers
- prtoection
- cells are dead
100
Stratum Granulosum characteristics
between s corneum and s spinosum
3-5 cell layers compacted and flattened
living cells that are re organizing keritin and associating it with flaggrin and other protiens
when they die they release lamellar granules which are lipid rich and help reduce water loss
101
Stratum Spinosum characterisitics
superficial to the s.
basale
▪ 8-10 cell layers – in most skin this
is the thickest layer
▪ Very thick in thick skin
- Very busy synthesizing keratin,
proto-filaggrin, and other proteins
▪ Eventually keratin becomes 50%
of the cell mass of keratinocytes
▪ Thick bundles of keratin called
tonofibrils are linked to
desmosomes
102
Stratum Basale function and characteristics
deepest epidermal layer
single layer
Stem cells divide and give rise to all of the layers
melanocytes
Wide range of sensory receptors
Resident immune cells
103
what are melanocytes
Synthesize and distribute
melanin to keratinocytes
104
describe the keratin structure
Fibrous protein – strong, often flexible long proteins that
have a relatively simple, repeating secondary structure
- have many hydrophobic amino acid residues that are insoluble in water
105
describe alpha keratin
alpha-helical protein with many levels of
structure:
Single “strand” protein arranged in an alpha helix
RIGHT HANDED COIL
106
what is a coiled coil of an alpha keratin
two strands coiled around eachother
LEFT HANDED
The two strands interact with each other at sites of
hydrophobic amino acid residues
Rich in alanine, valine, leucine, isoleucine, methionine,
phenylalanine (all hydrophobic)
107
what is a keratin Protofilament
long chains of two coiled coils
108
what is a keratin Protofibril
two long chains of protofilaments
109
what is hard keratin
just keratin with no fliaggrin or phospholipids
- hair and nails
110
what are the dermal layers from outermost to innermost
papillary layer
reticular layer
111
what are some characteristics of the papillary layer
superficial 1/5
interlocks dermis and epidermis
- papilla = " fingers"
- dermal papillae are vascularized
- also contains sensory receptors
112
what are some characteristics of the reticular layer
----- Usually thickest layer of the skin – thickest over the back
(4 mm)
houses:
- hair follicles
- nerves, arteries, veins and lymphatics
- sebaceous and sudoriferous sweat glands
- some adipose tissue
- smooth muscle cells
- some sensory receptors
113
coiled coil of an alpha keratin is ........ handed
left
114
alpha keratin is a ...... handed coil
right
115
what kind of CT is in the reticular layer
Dense irregular CT - type I collagen and elastic fibers
116
what kind of CT is the papillary layer made out of
Loose CT
- fine elastic fibers, type 3 and type 1 collagen
117
T or F dermal papillary layers are vascularized
T
118
what are fibril forming collagens
Type 1,2 and 3
119
type 1 collagen forms .... of the bodys collagen and has the most .....
90%
structural strength
120
what cell in the dermis produces collagens
fibroblast
121
where does assembly of the fibril forming collagens take place
extracellular space
122
Collagen is a .......... structure but is not a ......
coiled coil
a helix
123
what does a tropocollagen consist of
three collagen a chains are coiled around each-other
- themselves are twisted, not coiled
124
how is the tight twisting of the a-chains accomplished
unique amino acid structure
125
Gly -X -Y often collagen fiber X is
proline but not always
126
Gly -X -Y often collagen fiber Y is
hydroxyproline but not always
127
Hydroxyproline and proline have rigid
“kinked”
structures
These provide the sharp “twists” or “kinks”
in the molecule
128
Vitamin C is crucial to .......... and ......... of hydroxylated a.a.s
collagen formation
cross linking
129
fibroblasts produce ......... that have some degree of hydroxylation of glycosylation that are secreted into the ECM
tropocollagen fibers
130
outside of the cell, tropocollagen molecules are assembled into
fibrils and fibres
these fibers are also linked into proteoglycans and glycoprotiens
131
what is a hair follicule?
An epidermal in-growth into the
dermis (invagination) that builds a
long structure formed from hard
keratin = a hair
All hair follicles, although found
in the dermis, are derived from
the epidermis
Specialized keratinocytes
132
Are there areas of the skin completely
without hair?
* Palms and soles
* Lips, genital structures (glans penis,
labia minora, clitoris)
133
dermal papilla ....... the bulb supplying ....
contacts
capillary network
134
keratinocytes at the papilla are very similar to the ...... and spimosum
stratum granulosum
135
what is the spinosum (hair matrix) useful for
active site of cell division
- constantly going through mitosis
- constantly growing upwards
136
melanocytes in the blub transfer
melanosomes and keratinocytes
137
what are the three layers of the hair shaft
medulla
cortex
cuticle
138
medulla in the hair shaft is .......... the cortex is ......... in the cuticle the structure of ..... is more easily seen
lightly keratinized
filled with hard keratin
keratinocytes
139
technically it is not called a hair shaft until it passes beyond the ...
epidermis
140
what is the arrector pilli
a bundle of smooth muscle cells that pull the shaft into a more erect position
- innervated by the sympathetic nervous system, found on the same side as the sebaceous gland
141
what determines if you have straight or curly hair
the shape of the cortex
142
the hair root plexus has very .....
sensitive mechanoreceptors
- myelinated nerves
- desensitize rapidly
143
why does the arrector pili pull the shaft into a more erect position
prevent us from loosing heat too quickly
doesnt let the cold in
144
what are the three phases of hair growth
anagen
catagen
telogen
145
anagen is a .........
longer period of mitotic activity and growth
146
catagen arrested ........
growth and regression of the hair bulb
147
telogen is ........ often causing
cellular inactivity
hair shedding
148
at the begining of the next anagen phase ................
epidermal stem cells produce progenitors
149
progenitors give rise to the ...
matrix of the new hair bulb
150
stem cells are located in the ...... of the follicle, the external root sheath, near the attachement points of the arrector pilli
outer layer
151
hyposermis / subscutaneous tissue and superficial fascia is the ........ contains ....... and is important in ................. it is a ............ insulating against ......... The superficial region contains ......
Lower most layer
Contains loose areolar
and adipose tissue
Important in
stabilizing the position
of the skin in relation
to underlying tissues
Fat storage area,
insulates against
excessive heat loss
vessles
152
what colours skin
Hemoglobin: red
blood cells in
vasculature below
epidermis
If deoxygenation
occurs (hypoxia)
then the skin looks
relatively “blue” -
cyanosis
153
what is carotene
yellow
pigment from plants
in the diet
154
what is melanin
pale yellow
to black pigment
produced by
melanocytes
155
what do you call a flat lesion less than 5mm
macule
156
what do you call a flat lesion larger than 5mm
patch
157
what is a flat and raised lesion less than 5mm
papule
158
what is a flat and raised lesion called that is larger than 5mm
plaque
159
what is a solid bump with no fluid less than 5mm and more than 5mm
papule
nodule
160
what os a serous fluid filled lesion less than 5mm and larger than 5mm
vesicle and a bulla(e)
161
what is a puss filled lesion smaller than 5mm and larger than 5mm
pustule (cyst)
abbess or cyst
162
what is a scale
accumulation or excess shedding of the stratum
corneum – can be dry or waxy-feeling.
163
what is the result of defects in the moisture barrier (filaggrin) and tight junctions
antigens getting past the epidermal barrier over and over again
recruitment of immune cells
164
atopic dermatitis is noted by
edema in the epidermis
the lymphocytes and mast cells
hyperkeratotic skin
165
what is typically seen in psoriasis
epidermal hyper-proliferation and they divide very quickly
abnormal differentiation of epidermal keratinocytes
granulosa is absent
- enlarged blood vessels
166
what is vitiligo
disorder of skin pigmentation
immune system attacks the cells that produce melanin
167
what is alopecia areata
NK cells and cytotoxic T cells attack the hair follicle
patchy hair loss that does not scar and will re grow
168
what is an absess
a pocket of purulent fluid (bigger than a pustule) – not lined by epithelium
169
what is an ulcer
a defect in the epidermis, down at least to dermis level, usually due to impairment of healing/re-epithelialization
170
vascular lesions description
include telangiectasias (dilated arterioles, venules that one can
see with the naked eye) and hemangiomas (many different
types of vessel-rich, red or violet growths)
171
what is androgenetic alopecia
- hair loss over the crown
men posterior and lateral scalp
women
mid frontal hair loss
vertex temporal regions spared: frontal hair line
gradual conversion of terminal hairs to vellus hairs - inherited
greatly dependent on androgen exposure over time in men
androgens may less responsible in women
often larger psychosocial impact on women
172
what is acute telogen effluvium
non scarring alopecial characterized by acute / subacute diffuse hair shedding
metabolic or hormonal stress or by medications
- stressor causes anagen hair to enter telogen
recovery is spontaneous and occurs in 6 months
more chronic form also exists
173
was is reversible cell injury
a cell/tissue has been released, but overcomes this stress and resumes normal physiologic function
174
what is irreversible cell injury
a tissue/cell had beome damaged and will eventually die due to severity of the damage
175
what are the major concepts of apoptosis
initiation
- apoptotic signals recognized
- initiator caspases
execution
- capases are activated by the initiator and cause cellular changes and apoptosis
176
intristic apoptosis happens in the
mitochondrial pathway
177
extrinsic apoptosis happens in the
death receptor pathway
- outside of the cell
178
describe the extrinsic pathway
receptor ligand interactions (Fas and TNF receptor)
initiates caspases then exectioner capsases
179
intristic pathway results from ....... or from lack of .... results from increased permeability of the ......... with consequent release of death inducing molecules into the cytoplasm
cellular damage
growth factors
mitochondrial outer membrane
180
release of pro apoptotic protiens is highly controlled by the .......
BCL2 family of proteins
181
Bcl2 , Bcl x and Mcl-1 are ....
anti apoptotic
because of high levels in the presence of growth factors and other signals that indicate a viable cell
182
what is the role of anti apoptotic in prevention of apoptosis
keep the mitochondria from spilling out its guts
prevent mitochondrial pore formation and leakage of cytochrome c
183
Bax and Bak are ....
pro apoptotic
184
pro apoptotic can form .....
channels in the mitochondria and allow leakage
185
where are Bax and Bak formed?
3 "BH" domains called BH1-3
186
Bim, Bad , Bid, Puma and Noxa are increased when the cell is ...... or should undergo ...
stressed
apoptosis
187
how main domains have the BH domain
only one called BH3
188
what increases Bim, Bad , Bid, Puma and Noxa
ER stress
lack of growth signals
DNA damage
189
what activates the mitochondrial leak channel (Bax/Bak)
lack of BH4 molecules
presence of BH3 only molecules
190
what happens if you open the mitochondrial leak channel
cytochrome C leaks into cytosol
cytochrome C directly activates a protien known as apoptosis-activating factor (APAF) which causes an activation of caspases
191
the anti apoptotic and pro apoptotic Bh families ................
conteract eachother
the balance between the two will determine wether a cell will pursue apoptosis
192
what would be seen in a viable cell
survival (growth) factor present
production of anti apoptotic proteins present
BCL2 is being transported into the mitochondria
Cytochrome C is withheld in the mitochondria and there is no leakage
193
what would be found in an apoptotic cell
lack of survival signals
irrigation/ DNA damage
causing an activation of sensors BH3 only proteins
antagonism of BCL2
activation of BAX/BAK channel
leakage of cytochrome c
activation of caspases
apoptosis
194
apoptosis activating factor
stimulus cytochrome C
forming pores and releasing cytochrome C
Apaf1 associates with cytochrome C
assembly of an apoptosome (multiple units of a cytochrome C with Apaf1)
recruitment of caspase 9
activation of caspase 9 cleaves and activates exicution caspases
195
what are the key executioner caspases
3,6
9 is cleaved to activate them
196
initiated by activation of the plasma membrane death receptors on a variety of cells
extrinsic pathway
197
intracellular death domains of the extrinsic pathway
activate caspases 8 and 10
198
caspases 8 and 10 then activate
other caspases that are involved in the execution phase
199
Fas is a ...
death receptor
200
FasL is expressed on
immune T cells that recognise self antigens and some cytotoxic T cells
201
when FasL binds to Fas they form ...
a binding site called Fas- associated death domain (FADD) which activates caspases 8 and 10
202
both intrinsic and extrinsic pathways
converse in execution phase
203
caspases 8,9,10 can alla ctivate executioner caspases such as
3 and 6
204
executioner caspases can
cleavage of DNA
destroy nuclear matrix
destroy cytoskeletal changes
activated flipases
205
what is the end result of the execution phase
DNA is cut into discerete lengths by endonucleases activated by caspases
206
phosphitidylserine ... to the outer membrane
flips
allows macrophages to recognize and phagocytose
207
apoptoic pathways growht factods increase the synthesis od
Bcl-2 and Bclx
208
dna damage leads to the synthesis of....
p53
p53 stimulates Bax/Bak
209
misfolded proteins that accumulate in the ER cause ER stress which causes ...
production of caspases
210
with protein misfolding is very stressful for the ER ....
too much demand, beyond capacity
211
chaperone proteins are ...
ATP dependant
212
Necroptosis resembles necrosis but unlike necrosis
loose ATP
cell swelling
generation of free radicals
does not involve caspases activation
it is triggered by genetically programmed signal transduction
213
what is the mechanism of action for necroptosis
similar to extrinsic pathway binding of ligand to receptor
TNF tumor necrosis
RIP
214
hypertrophy is an increase
of cells which increase organ size
ex heart
215
what is hyperplasia
increase in the number of the cells in an organ
risk factor long term for malignancies
216
Atrophy is
a decrease in the numer or size of cells
loss of blood supply/ nerve supply
217
what are the three types of autophagy
chaperone mediated lyposomal digestion
macro autopahgy
218
what causes autophagy
cellular stresses such as nutrient depreviation activates autophagy through
initation
nucleation
elongation of isolation
219
where are autophagosome phagopores derived from?
the ER
220
phagopores are influenced by
initation and nucleating complex
causes it to surrond cellular components
221
autophagosome docks with
lysosome
222
what is pathogenic calcification
abnormal tissue deposition of calcium salts
223
what are the two forms of calcification
dystrophic
metastatic
224
what is dystrophic calsification
in dying tissue
usually present in atherosclerotic plaques
appear as macroscopically as fine white granules or clumps
225
in dystrophic calcification calcium is concentrated in ......... in cells by a process that is initiated by .......
membrane bound vesicles
membrane damge
226
what are the steps of dystrophic calcification
1. calcium ion binds to the phospholipids present in the vesicle membrane
2. phosphatases associated with the membrane generate phosphate groups which bind to the calcium
3. the cycle of calcium and phosphate binding is repeated, raising the local concentration and producing a deposit near the membrane
4. a microcrystal is formed which can lead to propagate and more calcium deposition
227
metastsic calcification
occurs in normal tissues due to diseases increases serum lelves
tends to affect intersitiual tisses of the gastic mucosa
tissues secrete acid at the surface of the cell
on the opposite surface, the cell is more alkaline
calcium precipitates in a more alkaline environment
228
what are the morphalogic patterns of necrosis (the 4 types)
1. coagulative
2. liquefactive
3. caseous
4. fat necrosis
229
what is coagulative necrosis
preservation of the basic outline of the coagulated cells
GHOST cells, no nuclei
effected tissue is firm
- most solid organs
230
nerotic cells are eventually removed by
fragmentation and phagocytosis of cellular debris
231
liquefactive neurois is
characterized by focal bacteria or funcgal infections acumulate inflammatory cells
completely digests dead cells
liquid viscous mass
232
caseous necrosis is
distinctive form of coagulative necrosis
cheesy in appearance
found often in TB infections (lung)
entire structure is known as gramuloma
no cell boarders - imflammatory border
233
fat necrosis is
not a specific pattern
- refers to a focal area of fat destruction
typically occurs as a result of release of activated pancreatic lipases into the pancreas and the peritonal cavity
visible chalky white areas
234
most necrotic cells and debris disappear with
combination of enzymatic digestion and fragmenation, followed by phagocytosis of debris by leukocytes
if not destroed and reabosrbed tend to atract calcium salts
235
types of insults to the cell or tissues
hypoxia and ischemia
infection, inflammation and immune mediated disorders
- toxins / chemical agents
- trauma , compression and thermal injuries
- deficiencies in nutrients or growth factors
236
the cellular response injury depends on
type of injury
duration of injury
severity of injury
the adaptability and metabolism/phenotype of the cell
237
what are some reverisble cell injuries
- cellular swelling
- non specific nuclear changes
- ribosomal detachment, membrane abnormalities die to cytoskeletal dissasembly, accumulation of lipids
- lipid vaculoles inlarge, collection of damaged membranous components
- loss of mRNA
- small bubble like outpouchings in the membrane
238
what are some reversible injuries that can not be seen
changes in calcium concentrations
unfolded proteins
damage to DNA or cytoskeletal elements
loss of membrane potentials or abnormal distribution of molecules across the cell membrane
ATP depletion
239
karolysis is
chromatin fades
240
pyknosis
chromatin condenses more basophillic, nucleous shrinks
241
karyorrhexis
nucleus fragments
242
necrosis is
the injured cell immediate loss of cellular viability
243
what can necrosis be caused by
depletion of ATP
mito damage
calcium accumulation
oxidative stress/free radicals
membrane damage
denatured proteins
DNA damage
244
how does ATP depletion cause cell injury
dysfunction and swelling of the sodium potassium pump
anaerobic metabolism decreases pH
increases production of free radicals
failure of calcium pumps
reduction in protein synthesis, detachment of ribosomes causing misfolding of proteins
245
calcium accumlation in the cell
activate variety of destructive enzymes
directly activate caspases
cause calcium release - decreased ATP
246
why is calcium a special ion
only ion that is ubiquitous second messanger
interacts with alot of intracellular proteins
247
mitochondrial damage
membranes can be damaged by free radical attack
cytosolic calcium increase too high in the cell MPTP can open
- loss of mitochondrial membrane potential
- releases H+
- further increase in cytoplasmic calcium
inability to generate ATP and ultimately necrosis
248
lipid breakdown can result in
leaky membranes
lipid breakdown
detergent like effects
- unesterfied free fatty acids
- acyl carnitine
- lysophospholipids
249
cytoskeletal abnormalities
activation of protases by increased cytosolic calcium
250
injury to lysosomes membranes results in
direct enzymatic damage by lysosomal enzymes
activation of enzymes by lysosomal enzymes
251
how are free radicals generated
normal metabolic processes
metabolism of drugs or toxins
radiation
fenton reaction - metals recieve or donate electrons
leukocytes
252
how is superoxide formed eliminated and what are the pathogenic effects
formed
- incomplete reduction of O2 during oxidative phosphorylation by phagocte oxidase in leukocytes
eliminated
conversion of H2O2 and O2 by SOD
pathogenic effects
production of degratative enzymes in leukocytes and other cells; may directly damage lipids , proteins and DNA
253
how is hydrogen peroxide formed, eliminated and what are the pathologic effects
formed
generated by SOD from O2 and by oxidases in peroxisomes
eliminated
conversion of H2O and O2 by catalase
pathologic
can be converted to OH and OCL which destroy microbes and cells
254
how id hydroxyl OH- formed, eliminated and what are the pathological effects
formed
generated from h20 by hydrolysis
eliminated
conversion to water by glutathione peroxidase
pathologic
most reactive oxygen derived free radical ; principle ROS responsible for damaging lipids, proteins and DNA
255
peroxynitrite formation, elimination and patholgic effects
formed
generated by O2 and NO synthase in many cell types
elimination
conversion to HNO2
pathologic
damages lipids , proteins and DNA
256
what is the fenton reaction
oxidation process activated by Fe(II) salts in the presence of H2O2 that generates radical species in solution and oxidizes a wide range of organic substrates with high activity but generally poor selectivity.
257
what are some mechanisms to remove free radicals
antioxidants
enzymes
258
if you black protein synthesis .... is blocked
apoptosis
259
what are some causes of apoptosis
programmed destruction
hormone dependant involution
cell deletion in proliferating cell populations
